Rare Rheumatology News

Disease Profile

Cerebrotendinous xanthomatosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

ageofonset-infancy.svg

ICD-10

E75.5

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

rnn-autosomalrecessive.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

CTX; Cerebral cholesterinosis; Sterol 27-hydroxylase deficiency

Categories

Congenital and Genetic Diseases; Digestive Diseases; Endocrine Diseases;

Summary

Cerebrotendinous xanthomatosis is a disorder characterized by abnormal storage of fats (lipids) in many areas of the body (lipid storage disease).[1] People with this disorder cannot break down certain lipids effectively (such as cholesterol), so these fats form fatty yellow nodules called xanthomas, that accumulate in the body, especially in the brain and the tendons that attach muscle to bone, which is reflected in the condition name (cerebromeaning brain and -tendinous referring to tendons). Symptoms may include diarrhea, clouding of the lens of the eyes (cataracts), tendon problems and progressive neurologic problems, such as epilepsy, movement disorders, impaired speech (dysarthria), loss of sensation in the arms and legs (peripheral neuropathy), dementia, hallucinations, and depression. Other symptoms may include brittle bones that are prone to fracture (osteoporosis) and an increased risk of developing heart or lung failure because of lipid buildup.[2][1] It is caused by mutations in the CYP27A1 gene. Treatment may involve chenodeoxycholic acid (CDCA), inhibitors of HMG-CoA reductase, coenzyme Q10 and surgery to remove cataracts.[1]

Symptoms

The symptoms seen in cerebrotendinous xanthomatosis are listed below. We have also included the typical age when each symptom appears.[1]

  • Chronic diarrhea (infancy)
  • Cataracts (early childhood)
  • Mental impairment (infancy or at puberty)
  • Xanthomas (adolescents to early adulthood)
  • Dementia with slow deterioration in intellectual abilities (early adulthood)
  • Spasticity (early adulthood)
  • Cerebellar signs such as intention tremor, difficulty with fast hand movements, nystagmus, truncal ataxia, and rhomberg's sign) (early adulthood)
  • Behavioral changes (early adulthood)
  • Hallucinations (early adulthood)
  • Agitation (early adulthood)
  • Aggression (early adulthood)
  • Depression (early adulthood)
  • Suicide attempt (early adulthood)

Other symptoms may include dystonia, atypical parkinsonism, seizures, and peripheral neuropathy.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of vision
Abnormality of sight
Vision issue

[ more ]

0000504
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Myoclonus
0001336
Xanthelasma
Fatty deposits in skin around the eyes
Fatty deposits on eyelids

[ more ]

0001114
30%-79% of people have these symptoms
Abnormal pyramidal sign
0007256
Abnormality of extrapyramidal motor function
0002071
Abnormality of the periventricular white matter
0002518
Angina pectoris
0001681
Atherosclerosis
Narrowing and hardening of arteries
0002621
Depressivity
Depression
0000716
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Dystonia
0001332
Hallucinations
Hallucination
Sensory hallucination

[ more ]

0000738
Hypercholesterolemia
Elevated serum cholesterol
Elevated total cholesterol
Increased total cholesterol

[ more ]

0003124
Hyperreflexia
Increased reflexes
0001347
Muscle weakness
Muscular weakness
0001324
Myocardial infarction
Heart attack
0001658
Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment

[ more ]

0002167
Peripheral neuropathy
0009830
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Tremor
0001337
5%-29% of people have these symptoms
Cerebral calcification
Abnormal deposits of calcium in the brain
0002514
Cholestasis
Slowed or blocked flow of bile from liver
0001396
Diarrhea
Watery stool
0002014
EEG abnormality
0002353
Joint dislocation
Joint dislocations
Recurrent joint dislocations

[ more ]

0001373
Joint stiffness
Stiff joint
Stiff joints

[ more ]

0001387
Malabsorption
Intestinal malabsorption
0002024
Nephrolithiasis
Kidney stones
0000787
Seizure
0001250
Percent of people who have these symptoms is not available through HPO
Abnormal circulating cholesterol concentration
Abnormality of cholesterol metabolism
0003107
Abnormality of central somatosensory evoked potentials
0100291
Abnormality of the dentate nucleus
0100321
Ataxia
0001251
Autosomal recessive inheritance
0000007
Cerebellar atrophy
Degeneration of cerebellum
0001272
Cerebral atrophy
Degeneration of cerebrum
0002059
Cholelithiasis
Gallstones
0001081
Delusions
0000746
Dementia
Dementia, progressive
Progressive dementia

[ more ]

0000726
EEG with generalized slow activity
0010845
EMG: axonal abnormality
0003482
Optic disc pallor
0000543
Osteoporosis
0000939
Pseudobulbar paralysis
0007024
Respiratory insufficiency
Respiratory impairment
0002093
Tendon xanthomatosis
0010874
Tuberous xanthoma
0031290

Cause

Cerebrotendinous xanthomatosis is caused by mutations in the CYP27A1 gene.[1]

Diagnosis

Yes, testing of the CYP27A1 gene is available. The Genetic Testing Registry provides information on clinical and research tests available for this condition.

Cerebrotendinous xanthomatosis is diagnosed by a combination of clinical features, cholestanol levels, and genetic testing. People with cerebrotendinous xanthomatosis have high levels of cholestanol in their blood. Genetic testing of the CYP27A1 gene is also available and can detect mutations in about 98% of patients.[1]

Treatment

Cerebrotendinous xanthomatosis may be treated with chenodeoxycholic acid (CDCA), which has been shown to normalize levels of cholestonal and improve neurologic symptoms. Inhibitors of HMG-CoA reductase may be used alone or in combination with CDCA. They are also effective in decreasing cholestanol concentration and improving clinical symptoms, however these treatments can lead to muscle damage. Coenzyme Q10 may improve muscle weakness, and cataract surgery may also be required.[1]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • Genetics Home Reference (GHR) contains information on Cerebrotendinous xanthomatosis. This website is maintained by the National Library of Medicine.
      • The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Cerebrotendinous xanthomatosis. Click on the link to view a sample search on this topic.

          References

          1. Federico A, Dotti MT, Gallus GN. Cerebrotendinous Xanthomatosis. GeneReviews. 2016; https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=ctx.
          2. Cerebrotendinous Xanthomatosis. Genetics Home Reference. 2016; https://ghr.nlm.nih.gov/condition/cerebrotendinous-xanthomatosis.

          Rare Rheumatology News